Control and/or quantification of target stimulation volume overlap and interface therefor

ABSTRACT

A method and system include a processor that outputs a characterization of a correspondence between a volume of estimated tissue activation and a target and/or side effect stimulation volume, and/or that provides controls by which to modify thresholds and/or amounts according to which the volume of estimated activation is to correspond to the target volume.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 15/181,286 filed Jun. 13, 2016, which is a continuation of U.S.patent application Ser. No. 13/570,736 filed Aug. 9, 2012, which issuedas U.S. Pat. No. 9,264,665, and which claims priority to U.S.Provisional Patent Application Ser. Nos. 61/521,572 filed Aug. 9, 2011,61/549,053 filed Oct. 19, 2011 and 61/651,282 filed May 24, 2012, thecontent of each of which is hereby incorporated by reference herein intheir entireties.

FIELD OF THE INVENTION

The present invention pertains to quantification and/or control ofoverlap of an estimated volume of tissue activated by a stimulation overa target volume of stimulation. Embodiments of the present inventionpertain to control and display of graphical user interfaces via which tocontrol (actual or simulated) a stimulation leadwire implanted in apatient and via which to view actual and/or estimated effects of aparameter set applied to the leadwire, in comparison with a targetvolume of activation. Aspects of the present invention pertain toleadwires and controls and displays thereof as described in U.S. patentapplication Ser. No. 12/454,330, filed May 15, 2009 (“the '330application”), U.S. patent application Ser. No. 12/454,312, filed May15, 2009 (“the '312 application”), U.S. patent application Ser. No.12/454,340, filed May 15, 2009 (“the '340 application”), U.S. patentapplication Ser. No. 12/454,343, filed May 15, 2009 (“the '343application”), U.S. patent application Ser. No. 12/454,314, filed May15, 2009 (“the '314 application”), U.S. Prov. Pat. App. Ser. No.61/468,884, filed Mar. 29, 2011 (“the '884 application”), U.S. Prov.Pat. App. Ser. No. 61/468,887, filed Mar. 29, 2011 (“the '887application”), U.S. Prov. Pat. App. Ser. No. 61/468,891, filed Mar. 29,2011 (“the '891 application”), U.S. Prov. Pat. App. Ser. No. 61/468,897,filed Mar. 29, 2011 (“the '897 application”), U.S. Prov. Pat. App. Ser.No. 61/468,901, filed Mar. 29, 2011 (“the '901 application”), and U.S.Prov. Pat. App. Ser. No. 61/521,626, filed Aug. 9, 2011 (“the '626application”), the content of each of which is hereby incorporated byreference herein in their entireties.

BACKGROUND INFORMATION

Electrical stimulation of an anatomical region, e.g., deep brainstimulation (DBS), such as of the thalamus or basal ganglia, or spinalcord stimulation (SCS) therapy, is a clinical technique for thetreatment of disorders such as essential tremor, Parkinson's disease(PD), and other physiological disorders. DBS may also be useful fortraumatic brain injury and stroke. Pilot studies have also begun toexamine the utility of DBS for treating dystonia, epilepsy, andobsessive-compulsive disorder.

A stimulation procedure, such as DBS, typically involves first obtainingpreoperative images, e.g., of the patient's brain, such as by using acomputed tomography (CT) scanner device, a magnetic resonance imaging(MRI) device, or any other imaging modality. This sometimes involvesfirst affixing to the patient's skull spherical or other fiducialmarkers that are visible on the images produced by the imaging modality.The fiducial markers help register the preoperative images to the actualphysical position of the patient in the operating room during the latersurgical procedure.

After the preoperative images are acquired by the imaging modality, theyare then loaded onto an image-guided surgical (IGS) workstation, and,using the preoperative images displayed on the IGS workstation, aneurosurgeon can select a target region, e.g., within the brain, anentry point, e.g., on the patient's skull, and a desired trajectorybetween the entry point and the target region. The entry point andtrajectory are typically carefully selected to avoid intersecting orotherwise damaging certain nearby critical structures or vasculature,e.g., of the brain.

In the operating room, the physician marks the entry point on thepatient's skull, drills a burr hole at that location, and affixes atrajectory guide device about the burr hole. The trajectory guide deviceincludes a bore that can be aimed to obtain the desired trajectory tothe target region. After aiming, the trajectory guide is locked topreserve the aimed trajectory toward the target region. After the aimedtrajectory has been locked in using the trajectory guide, a microdriveintroducer is used to insert the surgical instrument along thetrajectory toward the target region, e.g., of the brain. The surgicalinstrument may include, among other things, a recording electrodeleadwire, for recording intrinsic electrical signals, e.g., of thebrain; a stimulation electrode leadwire, for providing electrical energyto the target region, e.g., of the brain; or associated auxiliaryguidewires or guide catheters for steering a primary instrument towardthe target region, e.g., of the brain.

The stimulation electrode leadwire, which typically includes multipleclosely-spaced electrically independent stimulation electrode contacts,is then introduced to deliver the therapeutic stimulation to the targetregion, e.g., of the brain. The stimulation electrode leadwire is thenimmobilized, such as by using an instrument immobilization devicelocated at the burr hole entry, e.g., in the patient's skull, in orderfor the stimulation therapy to be subsequently performed.

The subthalamic nucleus (STN) represents the most common target for DBStechnology. Clinically effective STN DBS for PD has typically usedelectrode contacts in the anterior-dorsal STN. However, STN DBS exhibitsa low threshold for certain undesirable side effects, such as tetanicmuscle contraction, speech disturbance and ocular deviation. Highlyanisotropic fiber tracks are located about the STN. Such nerve tracksexhibit high electrical conductivity in a particular direction.Activation of these tracks has been implicated in many of the DBS sideeffects. However, there exists a limited understanding of the neuralresponse to DBS. The three-dimensional (3D) tissue medium near the DBSelectrode typically includes both inhomogeneous and anisotropiccharacteristics. Such complexity makes it difficult to predict theparticular volume of tissue influenced by DBS.

After the immobilization of the stimulation electrode leadwire, theactual stimulation therapy is often not initiated until after a timeperiod of about two-weeks to one month has elapsed. This is dueprimarily to the acute reaction of the tissue to the introducedelectrode leadwire (e.g., the formation of adjacent scar tissue), andstabilization of the patient's disease symptoms. At that time, aparticular one or more of the stimulation electrode contacts is selectedfor delivering the therapeutic stimulation, and other stimulationparameters are adjusted to achieve an acceptable level of therapeuticbenefit.

A system and method can estimate stimulation volumes, and display modelsof a patient anatomy and/or a stimulation leadwire, via which tographically identify the estimated stimulation volumes and how theyinteract with various regions of the patient anatomy, for example, asdescribed in the '330, '312, '340, '343, and '314 applications.

The systems and methods can be used to explore target regions ofstimulation and stimulation therapies to determine which therapy regimenis best suited for a particular patient or group of patients. The systemis configured to display a graphical user interface via which tovisually indicate a position of the leadwire in the patient anatomyand/or an actual or estimated effect of stimulation parameters appliedto the stimulation leadwire, for example in the form of a volume ofestimated activation (VOA), and/or via which to modify the parametersettings to be applied to the stimulation leadwire.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates representations of different scenarios of VOA andtarget region overlap and corresponding score function results,according to example embodiments of the present invention.

FIG. 2 is a graph plotting false positive scores against true positivescores of VOA to target region overlap, calculated for variousstimulation settings, according to an example embodiment of the presentinvention.

FIG. 3 is a screenshot of a graphical user interface for displayinganatomical, mechanical, electrical, and/or stimulation dependentcomponents, and stimulation controls, according to an example embodimentof the present invention.

FIG. 4 is a screenshot of a variation of the graphical user interface ofFIG. 3, with modified spill and overlap controls, according to anexample embodiment of the present invention.

FIG. 5 is a screenshot of a graphical user interface for displaying aleadwire control box and corresponding highlighting of selectedelectrodes, according to an example embodiment of the present invention.

FIG. 6 is a graph showing a relationship between volume overlap andspill at various stimulation settings.

FIG. 7 is a screenshot of a graphical user interface, in which a contactcontrol box is displayed for a selected contact, and stimulationparameters are displayed for non-selected contacts, according to anexample embodiment of the present invention.

DETAILED DESCRIPTION

Example embodiments of the present invention are directed to quantifyinga degree to which an estimated volume of activation (VOA) matchesanother obtained volume, such as, for example, a specified anatomicalvolume such as the sub-thalamic nucleus (STN), another VOA such as onewhich corresponds to another set of stimulation parameters, a sideeffect volume, and a target volume of activation, e.g., that is set withrespect to a particular stimulation therapy. The example embodimentsdiscussed below are discussed with respect to degree of match to atarget volume or side effect volume, but the discussion below similarlyapplies to other volume types. Example embodiments of the presentinvention also pertain to selection of a best VOA in accordance with aquantified similarity between each of a plurality of VOAs and anothervolume, such as the target volume of activation.

For example, a target volume can be manually or automatically obtained,e.g., as described in the '330, '312, '340, '343, '314, and '626applications (and can be output using systems described therein). Thetarget volume can be of a region of a patient's brain for DBS or otheranatomical region, e.g., for SCS. A VOA can be calculated and/or set asdescribed for example in the '330, '312, '340, '343, '314, and '626applications (and can be output using systems described therein). Thesystem is configured to compare a VOA corresponding to a set ofstimulation parameters, such as pulse width and/or voltage amplitude ofone or more electrodes of an implanted leadwire, to the target volume,and quantify the similarity between the VOA and target volume, e.g., inthe form of a degree of overlap of the volumes and/or spillover of theVOA beyond the boundaries of the target volume.

The following notations will be used below in discussions of targetvolumes and VOAs: V=VOA; and T=target volume of activation, where theVOA refers to a volume of tissue to be activated by application ofstimulation parameters to a leadwire implanted in a patient, for examplefor spinal cord or deep brain stimulation, and the target volumes arethose targeted to be activated. The VOA refers to an actually stimulatedregion or a region estimated to be activated in view of the appliedstimulation parameters. Additionally, side effect volumes of activationrefer to volumes where a side effect occurs or is estimated to occurbecause of the stimulation.

According to example embodiments of the present invention, a system andmethod includes consideration by a computer processor of one or more,e.g., all, of four kinds of subsets, including (1) V intersect T (i.e.,the area where the target volume and the VOA overlap), (2) V intersect Tcomplement (where T complement is everything in a considered anatomicalregion that is not within the target volume), (3) V complement intersectT (i.e., the area of the target volume with which the VOA does notoverlap), and (4) V complement intersect T complement (i.e., the area ofthe considered anatomical region in which neither the VOA nor the targetvolume fall). According to an example embodiment of the presentinvention, the system uses quantities of these four metrics to describeeverything about two data sets, i.e., a data set corresponding to theVOA and a data set corresponding to the target volume. Ideally V shouldagree with T, and their complements should agree with each other.

According to an example embodiment of the present invention, based onthe Jaccard index, the system is configured to calculate

$\begin{matrix}{\frac{V\bigcap T}{V\bigcup T},} & \left( {{eq}.\mspace{14mu} 1} \right)\end{matrix}$where ∩ symbolizes the intersection and ∪ symbolizes the union. That is,V∩T refers to the area that is common to both V and T, and V∪T refers tothe combination of the area that is within V and not within T, the areathat is within T and not within V, and the are in which T and V overlap.

Where the result of the calculation is 1, there is perfect agreementbetween T and V. Where the result of the calculation if 0, there is noagreements between T and V, i.e., this occurs where V∩T=0. A result thatfalls between 0 and 1 characterizes a degree of agreement between thevolumes that is greater than no agreement but less than perfectagreement.

According to an example embodiment of the present invention, the systemis configured to output the result of the calculation as acharacterization of the degree of agreement between the target volumeand VOA. For example, in a predefined mode of the system, as the usermodifies stimulation settings, the system is configured to responsivelyupdate a score displayed in a user interface.

For any voxel within the considered anatomical space, if the voxel iswithin both T and V, the voxel may be referred to herein as a truepositive; if the voxel is within both T compliment and V, the voxel maybe referred to herein as a false positive; if the voxel is within both Tand V complement, the voxel may be referred to herein as a falsenegative; and if the voxel is within both T complement and V complement,the voxel may be referred to herein as a true negative. Therefore, forexample, eq. 1 can be expressed as

$\frac{{true}_{—}{positives}}{{{true}_{—}{positives}} + {{false}_{—}{positives}} + {{false}_{—}{negatives}}}.$However, eq. 1 does not quantify or characterize true negatives. Thatis, eq. 1 indicates a ratio of the overlapping regions to thecombination of regions within either of the target volume and the VOA,but its result is not affected by a consistency of area not fallingwithin the considered volumes.

In an alternative example embodiment, based on the Rand index, thesystem is further configured to quantify a consistency between thetarget volume and VOA in a manner by which the quantification reflectstrue negatives. According to an example, the system is configured tocalculate

$\begin{matrix}{\frac{\left\lbrack {V\bigcap T} \right\rbrack + \left\lbrack {V^{c}\bigcap T^{c}} \right\rbrack}{\left\lbrack {V\bigcup T} \right\rbrack + \left\lbrack {V^{c}\bigcap T^{c}} \right\rbrack},} & \left( {{eq}.\mspace{14mu} 2} \right)\end{matrix}$where V^(c) is the area of V complement and T^(c) is the area of Tcomplement. Compared to eq. 1, eq. 2 adds true negative to both thenumerator and denominator. Specifically, the numerator includes allvoxels in which V and T agree and all voxels in which V^(C) and T^(C)agree; and the denominator includes all voxels in the considered area.

Where the result of the calculation using eq. 2 is 1, there is perfectagreement between T and V, and their compliments. However, where thereis no agreement between T and V, the result is usually not 0 becausethere usually is at least some agreement between V^(C) and T^(C).Instead, where there is no agreement between T and V, the result variesdepending on the area being considered, such that the greater the areabeing considered (and thus the greater V^(c)∩T^(c)), the greater theresult. Similarly, where there is some agreement between T and V andalso some agreement between V^(c) and T^(c), the result reflects boththe agreement between T and V and also the agreement between V^(c) andT^(c). According to an example embodiment of the present invention, thesystem is configured to output the result of the calculation as acharacterization of the degree of agreement between the target volumeand VOA and between their compliments.

An embodiment using eq. 2 is advantageous over an embodiment in whicheq. 1 is used because it is advantageous to assign a greater value forthose instances where there is more overlap of the complement areas. Onthe other hand, an embodiment in which eq. 1 is used is advantageousbecause of the simplicity of the characterization using a value between0 and 1 to indicate a degree of overlap.

However, the embodiments discussed above using eq. 1 or eq. 2 eachprovides for two very different scenarios a same respective score. Forexample, the two scenarios can be as shown in FIG. 1. In the firstscenario represented by part (a) of FIG. 1, V=10, T=10, and I=5, where‘I’ is the intersection of T and V. In the second scenario representedby part (b) of FIG. 1, V=15, T=5, and I=5, such that T is completelyincluded within V. Applying eq. 1 to each of the two scenarios providesa result of 5/15. (Further in this regard, the denominator in the firstscenario is 15 even though each of V and T is 10, because V and Toverlap at portion I, and portion I is counted just once. Similarly, thedenominator in the second scenario is 15 even though T is 5 and V is 15,because T corresponds to I and therefore completely overlaps V atportion I, and portion I is counted just once. Stated otherwise, in thesecond scenario, T can be ignored with respect to the denominator.)

Similarly, applying eq. 2 to each of the two scenarios provides a resultof

$\frac{5 + \left\lbrack {{{considered}_{—}{area}} - 15} \right\rbrack}{15 + \left\lbrack {{{considered}_{—}{area}} - 15} \right\rbrack}.$In this regard, eq. 2 differs from eq. 1 in that eq. 2 further considersthe true negative area V^(c) ∩T^(c), which is all of the considered areaexcept for any area that falls within any of T, V, and I (which is 15 inboth of the first and second scenarios, i.e., the true negatives in boththe first and second scenarios are the same).

That eq. 1 and eq. 2 do not differentiate between the first and secondscenarios, despite that so much less of V is external to T in the firstscenario than the second scenario, and despite that so much more of T isexternal to V in the first scenario than the second scenario, indicatesthat information is lost by these equations, i.e., informationrepresentative of such differences.

Accordingly, in an example embodiment of the present invention, thesystem and method quantifies a correspondence of V to T by plottingvalues representative of the correspondence in a receiver operatingcharacteristic (ROC) graph. FIG. 2 shows an example ROC graph. Forexample, the system calculates a true positive value and a falsepositive value, and plots in the ROC graph a point representative of theintersection of the calculated values, which intersection point is aquantification of the overlap of the VOA and the target volume. Forexample, the abscissa can be set to be representative of the falsepositive value and the ordinate can be set to be representative of thetrue positive value, as shown in FIG. 2. Such points have been plottedin the graph of FIG. 2 for a plurality of stimulation settings to obtaina curve, i.e., a ROC curve.

According to an example embodiment of the present invention, the truepositive value is

$\frac{V\bigcap T}{T}$and the false positive value is

$\frac{V\bigcap T^{c}}{T^{c}},$such that the true positive and false positive values will always fallat one of, or between, 0 and 1.

Generally speaking, as the value of a stimulation parameter, e.g., astimulation amplitude or pulse width, is increased, the size of the VOAincreases. Therefore, often the increase of the value of the stimulationparameter causes the overlap of the VOA over the area of the of thetarget volume to increase, but also causes the overlap of the VOA overT^(c) to increase. The ROC curve can be used to find a good balancebetween activating area belonging to the target volume and avoidingactivation of area belonging to the complement of the target volume. Forexample, parameters corresponding to point 1,1 on the ROC curve (where Vencompasses all of T and T^(c)) are usually undesirable, and parameterscorresponding to point 0,0 on the ROC curve (where V does not encompassany of T^(c), but also does not encompass any of T) are also usuallyundesirable. Accordingly, a point on the ROC curve that falls somewherebetween points 0,0 and 1,1, and the stimulation parameters correspondingto that point, can be selected as candidate parameters.

The ROC curve often includes a knee where the curve begins to slope moredrastically towards 1,1. Accordingly, the user viewing the ROC curveoutput by the system can select a point on the ROC to select idealstimulation parameters. For example, in an example embodiment, the ROCcurve is presented in a user interface in which the user is able to usean input device to select a point on the ROC curve, to which selectionthe system is configured to respond by selecting the parameterscorresponding to said selected point, as ideal stimulation parametersettings, either to be output as a suggestion to the clinician or toautomatically apply to the implanted leadwire. For example, the user canselect the point which appears to the user as most closely correspondingto the knee.

In an example embodiment, the system outputs a graphical representationof the VOA in an anatomical atlas space and/or overlapping arepresentation of the implanted leadwire and/or overlapping the targetvolume. The clinician can use the output information to determinewhether to use the suggested parameter settings or to tweak theparameter settings until the clinician finds favorable settings.

Thus, according to an example embodiment, the system outputs the ROCgraph, including the plotted curve, and the clinician can manuallyselect a point within the curve, in order to select the correspondingsettings. The system can responsively output the corresponding settingsand/or set the implanted leadwire according to the correspondingsettings, as discussed above, and/or can output a representation of thecorresponding volume as discussed above.

The curve can be constructed of points corresponding to many differentstimulation parameter combinations, including different combinations ofactive electrodes, different amplitude settings for the variouselectrodes, different pulse widths, etc. The system plots the points,and a knee point, and its corresponding parameters, can be selected, asdiscussed above. Additionally, different curves can be plot fordifferent selected stable settings, i.e., for each of the plottedcurves, the value(s) of one or more respective ones of the stimulationparameters are the same for all plotted values, the values of otherrespective parameters being changed. For example, different curves canbe plotted for different leadwire positions, i.e., the leadwire positionis the same for all plotted points of such a curve; or different curvescan be plotted for different pulse widths, i.e., the pulse width is thesame for all plotted points of the curve; etc. Any parameter can beselected as a stable parameter whose value remains the same for allplotted values of the respective curve.

In an example embodiment, different curves can be plotted for differentpatients. Thus, different points can be selected for different patients.This can be advantageous because the curves can be drastically differentfor different patients. For example, it can occur that for a firstpatient, the true positive and false positive values are the same formany or all parameter settings, such that the ROC curve is actuallyapproximately a straight line having a slope of 1, so that the ROC curvefor the patient provides no reason to increase the VOA, because theoverlap with T^(c) is increased at the same rate as the overlap with T.On the other hand, the ROC curve plotted for another patient can includea point at which the true positive begins to increase at a faster ratethan the false positive until an approximate leveling off of the slope.A different set of parameter settings would therefore be selected forthe second patient, due to the gain achieved by increasing the parametersetting to the curve point where this leveling off occurs.

Thus, the ROC curve(s) both quantify the T and V overlap and help withselection of optimal parameter settings.

According to an alternative example embodiment of the present invention,the system applies a mutual information formula to generate a scorerepresentative of the degree to which V corresponds to T. In thisregard, the probability that a random selected area, e.g., voxel,belongs to V is V/[total considered area]; the probability that itbelongs to T is T/[total considered area]; the probability that itbelongs to V^(c) is V^(c)/[total considered area]; the probability thatit belongs to T^(c) is T^(c)/[total considered area]; and theprobability that it belongs to I is I/[total considered area]. However,for example, given information that, for example, the random selectedarea belongs to T, can change the probability that it belongs to V. Forexample, if T=10 and 1=5, then, with such given information, theprobability that it belongs to V is 0.5. The mutual information formulaquantifies such effects on probabilities given the overlaps of thevarious considered areas (T, V, T^(c), V^(c)). That is, it quantifieshow information concerning one of the considered areas affects theprobabilities of the area belonging to others of the considered areas,and it characterizes how the partitioning of the area into T and T^(c)reflects the partitioning of the area into V and V^(c), and vice versa.

In the following, the braces { } indicate that reference is being madeto the partitions (the data set representing the volume and itscomplement), whereas the letters V and T, without the braces, indicatesthat reference is being made to the volumes themselves.

Formally, P(V) can be defined as the probability that a randomly chosenvoxel belongs in V, P(T) can be defined as the probability that arandomly chosen voxel belongs in T, P(V^(c)) can be defined as theprobability that a randomly chosen voxel belongs in V^(c), and P(T^(c))can be defined as the probability that a randomly chosen voxel belongsin T^(c).

Entropies (measures of unpredictability) for the partitions: {V} (i.e.,the set of V and V^(c)), {T} (i.e., the set of T and T^(c)), and {V,T}(i.e., the combination of the sets of V, V^(C), T, and T^(C)) can thenbe defined as:H({V})=−P(V)log_(e)(P(V))−P(V ^(C))log_(e)(P(V ^(C)))  (eq. 3);H({T})=−P(T)log_(e)(P(T))−P(T ^(C))log_(e)(P(T ^(C)))  (eq. 4); andH({V,T})=−P(V,T)log_(e)(P(V,T))−P(V,T ^(C))log_(e)(P(V,T ^(C)))−P(V ^(C),T)log_(e)(P(V ^(C) ,T))−P(V ^(C) ,T ^(C))log_(e)(P(V ^(C) ,T^(C)))  (eq. 5).

Mutual information can then be computed, according to an exampleembodiment of the present invention, as MI=H({T})+H({V})−H({V,T}) (eq.6). In an example embodiment, the computed mutual information value isoutput as a quantification of the correspondence between the targetvolume and the VOA.

In an example embodiment, the system calculates a normalized mutualinformation, which has a value of one of, or between, 0 and 1 or adifferent definition dependent maximum value that is less than 1. Thenormalized mutual information value can be calculated in a number ofalternative ways. For example, the normalized mutual information valuecan be calculated as

$\begin{matrix}{\frac{2{MI}}{{H\left( \left\{ V \right\} \right)} + {H\left( \left\{ T \right\} \right)}}.} & \left( {{eq}.\mspace{14mu} 7} \right)\end{matrix}$The resulting value indicates the degree of correspondence between theVOA and the target volume, where 0 represents no overlap, and 1 or adifferent definition dependent maximum value less than 1 corresponds toperfect overlap.

According to an alternative example embodiment, the system calculatesthe sum of the entropy of the two partitions ([T, T^(c)] and [V, V^(c)])minus twice the mutual information, i.e., H({T})+H({V})−2MI (eq. 8),which results in a score that can be normalized to a value at one of, orbetween, 0 and 1. This quantity measures the extent to which knowledgeof one partition reduces uncertainty about the other partition and isknown as the variation of information (see Marina Meila, “ComparingClusterings by the Variation of Information,” Learning Theory and KernelMachines: 173-187 (2003), which is incorporated by reference herein inits entirety). Note that variation of information may also be written asH(V|T)+H(T|V), i.e., the sum of the entropy of the T partition given theV partition and the entropy of the V partition given the T partition.

As discussed in, for example, the '330, '312, '340, '343, '314, and '626applications, certain anatomical regions, referred to herein as sideeffect regions, can be set as regions in which stimulation is preferablyavoided. While a VOA might closely match a target volume, it can alsooverlap a portion or all of one or more of such side effect regions.Selecting stimulation parameters can therefore include a balancingbetween meeting a target region and avoiding to some extent such sideeffect regions. According to an example embodiment of the presentinvention, the system is configured to calculate a measure of acorrespondence of a VOA to a target region and also to calculate ameasure of a correspondence of the VOA to one or more side effectregions. Based on output of such measures, a user can select stimulationsettings that provide a VOA that strikes a good balance betweenobtaining a good correspondence between the VOA and the target regionand a weak correspondence between the VOA and the one or more sideeffect regions. For example, the system can calculate the correspondencebetween the VOA and the side effect regions using any of the methodsdescribed above, e.g., eq. 1, eq. 2, the ROC graph/curve, the mutualinformation formula, or the entropy formula.

According to an example embodiment of the present invention, the systemplots the target overlap and side effect overlap scores for a pluralityof stimulation settings in a shared graph space. For example, theabscissa can correspond to the sets of stimulation settings for whichthe scores have been calculated and the ordinate can correspond to thescore, or vice versa. According to an example of this embodiment, thesystem is configured to connect the plotted target region scores to forma first curve and to connect the plotted side effect region scores toform a second curve. According to an example of this embodiment, thesystem is configured to graphically identify whether a plotted score isassociated with the target region or with the side effect region. Forexample different colors, hatching, or size of the nodes and/orconnecting lines can be used for differentiation. The user is therebyvisually informed of the correspondence between target and side effectregion overlap for the different settings. The user is then able toselect those settings which the user determines provides the besttrade-off between target region overlap and side effect regionavoidance. For example, in an example embodiment, the system providesthe integrated graph in a user interface in which the user is able toselect a point within the graph corresponding to one of the sets ofparameter settings. Responsive to such selection, the system isconfigured to display information regarding the selected settings, e.g.,amplitude, pulse width, rate, electrode combination, etc.; and/ordisplay the corresponding VOA, e.g., in spatial relation to the targetregion and/or side effect region(s), and/or in spatial relation to agraphical representation of the implanted leadwire, and/or in spatialrelation to anatomical structures, e.g., atlas structures and/or medicalimage structures. Alternatively or additionally, the system responds tothe selection by programming the implanted pulse generator (IPG) withthe selected settings. Alternatively, the interface includes a separateselectable input element, in response to selection of which, the systemprograms the IPG with the selected settings.

According to the embodiment in which the ROC curves are plotted for thetarget and side effect region overlap, in an example embodiment, inorder to visually indicate the correlation between the curves for thetarget region(s) and side effect region(s), the system plots the scoresin a three-dimensional coordinate space, where a first axis correspondsto the false positive score, a second axis corresponds to the truepositive score, and the third axis corresponds to the stimulationsettings for which the scores were calculated. Alternatively, the systemoutputs a separate, e.g., two-dimensional, graph for each set ofparameter settings for which the scores are calculated, where one of theaxes corresponds to the false positive scores and another of the axescorresponds to the true positive scores, but where all plotted scores ofthe respective graph correspond to a single one of the sets of parametersettings. The user can then select the graph which includes thoseplotted points the user determines reflects the best trade-off betweenmatching the target volume(s) and avoiding the side effect volume(s).

It is noted that there may be more than one target region. In an exampleembodiment, the system treats the multiple regions as multiplesub-regions of a single target region for which a respective score iscalculated and output. Alternatively, the system calculates a singlecomposite target region score based on the scores for the multipletarget regions, e.g., an average of the scores. According to an examplevariant of this embodiment, the system differently weights differentones of the target regions. For example, one target region can be set asbeing more important than another target region, and the systemtherefore assigns a greater weight to the score calculated for the moreimportant region. For example, different target regions may beassociated with different therapeutic effects, which effect theirimportance. (The system can similarly calculate a single side effectregion score based on scores calculated for multiple side effectregions. Further, different side effect regions can be differentlyweighted, e.g., because of the type or severity of the side effects withwhich they are associated.)

As noted above, in an example embodiment, separate scores are calculatedand output for each of the target regions. Their scores can be plottedin a graph, one of whose axes corresponds to the sets of stimulationsettings. The user can then select the settings providing the bestbalance between coverage of the multiple target regions. According tothe embodiment in which an ROC graph is output, a three-dimensionalgraph may be output, where one of the axes corresponds to the sets ofstimulation settings. Alternatively, a different graph can be output foreach set of stimulation settings for which the calculations are made.

According to an example embodiment of the present invention, the systemcalculates for a set of stimulation settings a single score based on thescores calculated for the one or more target regions and the one or moreside effect regions. For example, an average or weighted average of allof the scores can be calculated, e.g., where the side effect regionscores are assigned a negative value and the target region scores areassigned a positive value. The different target and side effect regionscan be weighted differently, as noted above. According to an embodimentin which the ROC graph is used, a single composite true positive scorecan be calculated and a single composite false positive score can becalculated for a single set of stimulation parameters, based on theoverlap and/or spill of a plurality of target and side effect regions,where, for example, the side effect regions are assigned a negativevalue for their true positive scores and a positive value for theirfalse positive scores and vice versa for the target regions. Accordingto this embodiment as well, different regions can be differentlyweighted.

According to an example embodiment of the present invention, a systemincludes a processor that is configured to obtain one or more medicalimages, e.g., magnetic resonance image (MRI) or computed tomography (CT)image, of an anatomical region of a patient, and display the image(s) oran anatomical atlas conforming to the image(s) in a graphical userinterface (GUI). The image can be one taken after implantation of aleadwire, such that the leadwire is displayed in the image.Alternatively (or additionally), a leadwire model can be superimposed bythe processor over a part of the displayed image corresponding to thelocation of the leadwire in the anatomical region of the patient. In anexample embodiment, the GUI includes controls for controllingstimulation parameters to be set for the electrodes (also referred toherein as “electrode contacts”) of the leadwire (also referred to hereinas “lead”), for actual programming of the leadwire to stimulate aportion of the displayed anatomical region of the patient and/or forsimulation of such stimulation. In an example embodiment of the presentinvention, the processor is configured to provide in the GUI a legendthat identifies, e.g., by color coding or hatching, various structuresof the displayed image or atlas, to help the user better understand therelative positions of significant structures within the display, e.g.,relative to the leadwire or one or more of the displayed anatomicalstructures.

FIG. 3 shows a GUI according to an example embodiment of the presentinvention. The GUI includes a display of an atlas of a region of apatient's brain. The displayed atlas (and/or medical image) can be twodimensional or three dimensional. In FIG. 3, it is three dimensional.Although the features described with reference to FIG. 3 pertain to thebrain, the features can similarly be provided with respect to anyanatomical region of a patient. Additionally, while FIG. 3 shows anatlas of a brain that has been conformed to medical images of a user,the features can similarly be applied to the actual medical images, byoverlaying the described controls and graphical elements over themedical images.

The displayed atlas includes representations of a plurality ofanatomical structures. They include a sub-thalamic nucleus (STN) graphic114, a thalamus graphic 118, a red nucleus graphic 120, a globuspallidus graphic 122, and an optic nerve graphic 124. FIG. 3 is agrayscale image. However, the GUI can be presented in color, and thegraphics representing the different anatomical structures can bepresented in different colors to more clearly identify their boundaries.For example, the STN graphic 114 can be displayed in bright green, thethalamus graphic 118 can be displayed in grey, the red nucleus graphic120 can be displayed in a muted red, the globus pallidus graphic 122 canbe displayed in a muted green, and the optic nerve graphic 124 can bedisplayed in yellow. Where structures overlap each other, theoverlapping structures can each be discernible using appropriatetransparency levels.

In an example embodiment, and as shown in FIG. 3, the GUI furtherincludes a structure menu 100 that includes a listing, e.g., by name, ofone or more, e.g., all, of the separately represented structures, whereeach listing is displayed immediately adjacent a swatch of the colorused for its representation. For example, “STN” can be displayedimmediately adjacent a swatch of bright green, represented in thegrayscale image of FIG. 3 as a bright box. As shown in FIG. 3, thelisting can be divided into different sections that each corresponds toa respective category of information. For example, the top section ofthe structure menu 100 in FIG. 3 can include those displayed structuresthat are considered most relevant to the therapeutic stimulation beingstudied or applied, and the bottom section can include those displayedstructures that are considered less relevant to the therapy. What isconsidered most relevant to the therapy can be predetermined, e.g.,based on the patient's condition, such as whether the patient is a PD orAlzheimer's patient, or can be set by the clinician.

Instead of or in additional to displaying the different structures usingdifferent colors or shades, the system can use different respectivehatchings for their display. The swatches of the structure menu 100 canaccordingly show the respective hatchings.

Besides for anatomical structures, the processor can display in the GUIdefined relevant mechanical and/or electrical structures. For example,FIG. 3 includes a lead graphic 116 representing the implanted leadwireand displayed in a bright blue, and a contact graphic 125 for eachelectrode contact of the leadwire, displayed in yellow. The structuremenu 100 can further identify one or more of such mechanical and/orelectrical structures. For example, the structure menu 100 of FIG. 3lists “lead” adjacent a swatch of the color used for its representation.

In an example embodiment of the present invention, the system displaysdefined stimulation regions. For example, a user or system selectedand/or defined target region, which, as described above, is an idealarea targeted for stimulation, can be displayed with a target regiongraphic 110. Additionally (or alternatively) a volume of estimatedactivation (VOA) for a given stimulation parameter set can be displayedwith an active simulation graphic 112. Such areas can also be displayedwith respective colors and/or hatchings. For example, the target regiongraphic 110 can be displayed in bright blue and the active simulationgraphic 112 can be displayed in bright red. The structure menu 100 canalso include a listing of one or both (or none) of these structuresadjacent respective swatches of their respective colors and/orhatchings.

In an example embodiment of the present invention, the GUI isuser-interactive, e.g., by point and click using an input device such asa mouse, stylus, or even the user's finger, or by keyboard manipulation,for selecting and deselecting the text listings and/or theircorresponding swatches in the structure menu 100, in accordance withwhich the system adds or removes the respective color and/or hatching ofthe structure corresponding to the selected item of the structure menu100. For example, while the STN graphic 114 is displayed in brightgreen, the user can select its corresponding swatch or label in thestructure menu 100, in response to which selection, the system updatesthe GUI so that the STN graphic 114 is no longer displayed with thatcolor. This may be helpful to allow the user to highlight those of theincluded structures that are of interest to the user, the otherstructures essentially becoming background by their grayscale, black, orother similar presentation.

In an example embodiment of the present invention, the GUI includescontrols for modifying the stimulation settings of the electrodecontacts, actually and/or virtually as proposed changes in a simulationto study the effects of the proposed changes to the settings on thestimulation. According to example embodiment, the system calculatesscores as discussed above based on estimated overlap with one or moretarget and/or side effect regions.

According to an example embodiment of the present invention, the GUIincludes a spill control 103 that can be manipulated by the user toslide along a spill bar 102 and/or includes an overlap control 105 thatcan be manipulated by the user to slide along an overlap bar 104. Whereboth are provided, manipulation of one may cause an automatic change ofthe position of the other.

The spill control 103 can be manipulated to change the amount of allowedspill of the VOA beyond the boundaries of the target region. Forexample, referring to FIG. 3, the spill control 103 can be shifted tothe right to increase the amount of spill, and to the left to lower theamount of spill. In an alternative example embodiment, an exact amountof spill is not increased or lowered; rather, a threshold is raised orlowered. For example, according to this embodiment, the spill control103 can be shifted to the right to raise the threshold of maximumallowed spill, and to the left to lower the threshold of maximum allowedspill.

In this regard, it is often not possible to set stimulation parametersof the electrode contacts to produce a region of activated tissue thatcorresponds exactly to the target region of stimulation. Whileincreasing the amplitude of settings of one or more electrode contactsmay produce a larger estimated stimulation region to fill a greateramount of the target region, such increase of amplitude often results ina larger amount of the estimated stimulation region that extends beyondthe boundaries of the target stimulation region at one or morelocations. Increasing the threshold amount of allowed spill thereforeoften allows the system to suggest stimulation parameters for filling agreater amount of the target stimulation region. In an exampleembodiment of the present invention, in response to the user sliding thespill control 103 to revise the spill threshold, the system accordinglymodifies the spill threshold, finds a set of stimulation parametersthat, if applied to the electrode contacts, is estimated to provide thegreatest fill of the target region while not exceeding the spillthreshold, and modifies the active simulation graphic 112. In an exampleembodiment, one or more electrode contacts and/or overall leadwireparameter settings can be displayed. According to this embodiment, thesystem can also update such settings in response to the user's slidingof the spill control 103, where such change results in a differentparameter set.

The overlap control 105 can be similarly operated to increase ordecrease the amount of the target region to be filled. According to analternative example embodiment of the present invention, the overlapcontrol 105 can be operated to raise or lower a threshold of overlap,according to which the overlap amount can be increased or decreased.

The increase of the amount of the target region to be filled may (butnot necessarily) require a reduction of the spill threshold. Forexample, the user can slide the overlap control 105 to the right as aninstruction to modify the stimulation settings so that the VOA fills agreater amount of the target region (where such parameters arefeasible), but such modification of the stimulation settings may resultin a VOA that spills over beyond the boundaries of the target regionmore than the set spill threshold. Accordingly, in such an instance,according to an example embodiment, the system automatically adjusts thespill amount/threshold in response to the user's instruction. Where thishappens and the system finds parameters that would produce a VOA thatmore completely fills the target region as instructed by the user, andin an embodiment in which the spill control 103 is displayed besides forthe overlap control 105, the system accordingly shifts the spill control103 to the right along spill bar 102, and adjusts the active simulationgraphic 112 accordingly.

Similarly, the decrease in allowed amount of spill set byuser-manipulation of the spill control 103 may (but not necessarily)require a reduction in required overlap. Accordingly, in such aninstance, according to an example embodiment, the system automaticallyadjusts the overlap amount/threshold in response to the user'sinstruction, and, according to an example embodiment, automaticallyadjusts a position of the spill control 103.

According to the embodiment in which the overlap control 105 correspondsto an overlap threshold, in an example embodiment, the overlap thresholdis a minimum percentage of the target volume with which the VOA is tooverlap. For example, in an example embodiment, for a minimum overlapthreshold set by user-manipulation of the overlap control 105, thesystem determines the set of stimulation parameters that provides a VOAthat meets the set minimum overlap threshold with the least spill.Similarly, in response to user-manipulation of the spill control 103,the system determines the set of stimulation parameters that provides aVOA that meets the set maximum spill threshold with the most overlap.According to an alternative example embodiment of the present invention,in response to a shift of the spill control 103 or a shift of theoverlap control 105, the system determines a set of stimulationparameters that provides a best of possible VOAs (corresponding todifferent possible sets of stimulation parameters) that meets thethresholds, where what is considered best depends on a score calculatedfor the VOA, e.g., according to one of the scoring methods describedabove (which can include consideration of side effect regions as well).

According to an alternative example embodiment, the overlap threshold isa maximum percentage of the target volume with which the VOA is tooverlap. In response to user-manipulation of the overlap control 105,the system determines the set of stimulation parameters that provides aVOA with the most overlap not exceeding the maximum threshold.Alternatively, the system determines the set of stimulation parametersthat provides a VOA having the best score of VOAs meeting the maximumthreshold, for example, where the score is determined using one of themethods described above (which can include consideration of side effectregions as well).

According to an alternative example embodiment, whether the setthreshold is a minimum or a maximum depends on a direction in which theuser moves the overlap control 105. For example, if the user shifts theoverlap control 105 to increase the threshold, then it is treated as aminimum threshold, and if the user shifts the overlap control 105 todecrease the threshold, then it is treated as a maximum threshold.

According to an example embodiment, where the user slides the overlapcontrol 105 to increase the fill amount by more than is feasible, thesystem finds the parameters that produces the greatest fill amount, andautomatically adjusts the position of the overlap control 105accordingly. Similarly, where the user slides the spill control 103 toincrease the spill threshold by an amount not required to obtain thegreatest feasible fill amount of the target region, according to anexample embodiment, the system adjusts the spill threshold to the spillamount required for the greatest fill amount of the target region.

In an example embodiment of the present invention, the system textuallyquantifies the spill amount and/or overlap amount. For example, FIG. 3shows that the spill amount is 18% (and that the amount by which the VOAdoes not spill beyond the target region is 82%), and that the overlapamount is 48% (and that the amount by which the VOA does not overlap is52%). The spill amount can be expressed as a percentage of the VOA, andthe overlap amount can be expressed as a percentage of the targetregion. For example, with reference to FIG. 3, 82% of the VOA is withinthe target region and 18% of the VOA spills beyond the boundaries of thetarget region; and 48% of the target region is filled by the VOA and 52%of the target region is not filled by the VOA. According to analternative example embodiment, the spill corresponds to

$\frac{V\bigcap T^{c}}{T^{c}}$and is therefore dependent on a predefined considered area in which theVOA and target regions can be positioned.

Alternatively, other measures can be used. For example, the system canexpress the amounts as any number between 0 and 1. With respect to spillamount, the system can, for example, determine the greatest technicallyand/or safely feasible VOA and set the spill amount of 1 as representingthe spill resulting by such settings. Similarly, with respect to overlapamount, the system can, for example, determine the greatest amount ofthe target region that can technically and/or safely possibly be filled,and set the overlap amount of 1 as representing such a fill amount.

FIG. 4 shows an alternative example embodiment of the spill and overlapbars and controls. In FIG. 4, an overlap control 205 is displayed as aterminal of an overlap bar 204, and can be dragged upwards or downwardsto correspondingly lengthen or shorten the overlap bar 204 andcorrespondingly raise or lower the overlap amount. Similarly, a spillcontrol 203 is displayed as a terminal of a spill bar 202, and can bedragged downwards or upwards to correspondingly lengthen or shorten thespill bar 202 and correspondingly raise or lower the spill amount. Othergraphical representations can be used instead. For example, the controls203 and 205 can be omitted, and the bars themselves can be dragged inone of the directions to change their respective lengths. Alternatively,arrows can be displayed and selectable for changing the lengths of thebars. Alternatively, the lengths can be modifiable by manipulation ofkeys of a keyboard without manipulation of a graphical control.

In an example embodiment of the present invention, the system recordsthe spill and overlap amounts of each of a plurality of stimulationsparameter sets actually applied or simulated over time, and generatesand outputs to the user a graph, as illustrated in FIG. 6, showing thedifferent spill levels, overlap levels, and/or differences therebetween.The user can use such information, for example, in deciding the level ofoverlap to try to attain. In the graph of FIG. 6, the line beginning atapproximately 40 represents the overlap amount, the line beginning justbelow 10 represents the spill amount, and the line beginning just above30 represents the difference between the overlap and spill amounts. Forexample, the spill curve can plot percentages of respective VOAs(corresponding to the settings corresponding to one of the axes of thegraph) that spill beyond the target volume, the overlap curve can plotpercentages of the target volume that are overlapped by the respectiveVOAs, and the difference curve can plot the differences between thosevalues. Alternatively, the spill curve can plot the values of

$\frac{V\bigcap T^{c}}{T^{c}}$calculated for the different settings and the overlap curve can plot thevalues of

$\frac{V\bigcap T}{T}$calculated for the different settings. The latter embodiment may beadvantageous because the same area is considered for evaluating thespill values for the different VOAs, whereas according to the formerembodiment, the percentages are of the complete volume of each of theVOAs themselves, and are consequently percentages of different sizedvolumes. According to yet another embodiment, the spill values of thespill curve are numbers of voxels of the respective VOAs that do notoverlap the target volume, and the overlap values of the overlap curveare numbers of voxels of the respective VOAs that overlap the targetvolume. Whichever calculations are used for obtaining the spill andoverlap values, the difference curve plots the differences between thosecalculated values for a plurality of sets of stimulation parameters.

Alternatively, scores can be calculated and output, e.g., in graphs, asdescribed above, e.g., using eq. 1, eq. 2, the ROC graph(s), the mutualinformation formula, or the entropy formula.

Referring again to FIG. 3, in an example embodiment of the presentinvention, the system is configured to display a contact control box 106within, e.g., overlaid on, the anatomical atlas/image for modifying theparameters of a respective electrode contact. For example, a separaterespective contact control box 106 can simultaneously be displayed foreach of the electrode contacts. Alternatively, each of the contactgraphics 125 can be separately selectable, in response to whichselection the respective contact control box 106 corresponding to theselected contact graphic 125 is selectively displayed, the others notbeing displayed. Alternatively, when none of the electrode contactgraphics 125 are selected, the system omits from the display all of thecontact control boxes 106, and when any one of the contact graphics 125is selected, the system responsively displays all of the contact controlboxes 106, since the settings of one contact may affect the user'sdecision as to how to set another of the contacts. According to thisembodiment, after the contact is selected, the user can deselect, e.g.,by selecting any part of the GUI other than any of the contacts graphics125 and contact control boxes 106, or by reselecting the same contactgraphic 125.

In an example embodiment, the user can interact with displayedcomponents of the displayed contact control box 106 to modify thesettings of the electrode contact to which it corresponds. Suchinteraction can be, for example, by way of mouse, stylus, finger, orkeyboard entry.

In an example embodiment of the present invention, the control elementsdisplayed within the contact control box 106 are limited to only thosewith which interaction provides for modification of respective settingsof the particular electrode to which it corresponds. Control elementsfor modifying settings of the leadwire as a whole and that are notspecific to any one electrode can be displayed in a separate region ofthe GUI. For example, FIG. 3 shows display of such controls at the leftside of the GUI separate from the anatomical image and/or atlas display.

In an example embodiment of the present invention, responsive toselection of one of the contact graphics 125, the system modifies thedisplay of the selected contact graphic 125. For example, it can bedisplayed with a different color or in a different, e.g., brighter,shade of the same color, to visually indicate to the user which contacthas been selected and/or for which the contact control box 106 isdisplayed.

In an example embodiment of the present invention, even where only asingle contact control box 106 corresponding to a selected one of thecontact graphics 125 is displayed, one or more presently set settings ofthe other contacts are displayed in the anatomical image and/or atlasalongside the respective other contacts and/or with a connector from thedisplayed settings to the respective contacts to which they correspond,e.g., as shown in FIG. 7.

In an example embodiment of the present invention, the system displays aleadwire control box 500 in the GUI, e.g., beside the anatomical imageand/or atlas, e.g., as shown in FIG. 5. The leadwire control box 500 caninclude controls for modifying various settings of the leadwire and itselectrode contacts. The leadwire control box can include a model of theleadwire, including respective electrode components representing each ofthe electrode contacts of the leadwire. Each of the displayed electrodecomponents can be separately selectable, in response to which selectionthe selected electrode component is highlighted and its settings can bemodifiable by interaction with other displayed controls. In an exampleembodiment, besides for or instead of highlighting the selectedelectrode component of the model leadwire of the separate leadwirecontrol box 500, the respective contact graphic 125 displayed in theanatomical image and/or atlas is highlighted in response to theselection of the electrode component in the leadwire control box 500,thereby visually informing the user of the relationship of the selectedelectrode to the displayed anatomical image and/or atlas. In an exampleembodiment, the respective contact control box 106 corresponding to theselected electrode contact can be displayed in addition to or instead ofthe control elements of the leadwire control box 500 for controlling thespecific electrode that has been selected.

The various methods described herein can be practiced, each alone, or invarious combinations.

An example embodiment of the present invention is directed to aprocessor, which may be implemented using any conventional processingcircuit and device or combination thereof, e.g., a Central ProcessingUnit (CPU) of a Personal Computer (PC) or other workstation processor,to execute code provided, e.g., on a hardware computer-readable mediumincluding any conventional memory device, to perform any of the methodsdescribed herein, alone or in combination. In certain exampleembodiments, the processor may be embodied in a remote control device.The memory device may include any conventional permanent and/ortemporary memory circuits or combination thereof, a non-exhaustive listof which includes Random Access Memory (RAM), Read Only Memory (ROM),Compact Disks (CD), Digital Versatile Disk (DVD), and magnetic tape.

An example embodiment of the present invention is directed to a hardwarecomputer-readable medium, e.g., as described above, having storedthereon instructions executable by a processor to perform the methodsdescribed herein.

An example embodiment of the present invention is directed to a method,e.g., of a hardware component or machine, of transmitting instructionsexecutable by a processor to perform the methods described herein.

An example embodiment of the present invention is directed to an outputdevice configured to output any of the GUIs described herein.

The above description is intended to be illustrative, and notrestrictive. Those skilled in the art can appreciate from the foregoingdescription that the present invention can be implemented in a varietyof forms, and that the various embodiments can be implemented alone orin combination. Therefore, while the embodiments of the presentinvention have been described in connection with particular examplesthereof, the true scope of the embodiments and/or methods of the presentinvention should not be so limited since other modifications will becomeapparent to the skilled practitioner upon a study of the drawings,specification, and the following claims.

What is claimed is:
 1. A system for selecting electrical stimulationparameters, comprising: a processor configured to perform actions, theactions comprising: obtaining a volume of activation (VOA) of tissueestimated to be activated by stimulation provided according to a set ofstimulation parameters; obtaining a second volume; generating a firstscore for the VOA based on a) an amount by which the VOA overlaps thesecond volume and b) at least one of the following listed quantities: 1)a size of the second volume; 2) a size of an area formed by combinationof the VOA and the second volume, 3) a size of a predetermined areaexcluding both the VOA and the second volume, 4) an amount of the VOAthat does not overlap the second volume, or 5) an amount of the secondvolume that does not overlap the VOA; and upon user request, outputtinga set of stimulation parameters corresponding to the VOA to initiatestimulation of patient tissue using a leadwire implanted in the patienttissue.
 2. The system of claim 1, wherein the second volume is either a)a specified anatomical volume, b) another VOA estimated to be activatedby stimulation provided according to another set of stimulationparameters, c) a side-effect volume, or d) a target volume ofactivation.
 3. The system of claim 1, wherein the first score is basedon at least two of the following listed quantities: 1) the size of thesecond volume; 2) the size of the area formed by combination of the VOAand the second volume, 3) the size of the predetermined area excludingboth the VOA and the second volume, 4) the amount of the VOA that doesnot overlap the second volume, or 5) the amount of the second volumethat does not overlap the VOA.
 4. The system of claim 1, wherein: thegenerating of the first score includes calculating$\frac{V\bigcap T}{V\bigcup T};$ V represents the VOA; T represents thesecond volume; ∩ represents intersection; and ∪ represents union.
 5. Thesystem of claim 1, wherein: the generating of the first score includescalculating $\frac{V\bigcap T}{T};$ V represents the VOA; T representsthe second volume; and ∩ represents intersection.
 6. The system of claim1, wherein the actions further comprise generating a second score forthe VOA based on an amount by which the VOA overlaps an obtained sideeffect volume in which stimulation is to be avoided.
 7. The system ofclaim 6, wherein the second score is generated further based on a sizeof an area formed by a combination of the VOA and the obtained sideeffect volume.
 8. The system of claim 1, wherein the first score isfurther based on an amount by which the VOA overlaps an obtained sideeffect volume in which stimulation is to be avoided.
 9. The system ofclaim 1, wherein: the generating of the first score includes calculating$\frac{\left\lbrack {V\bigcap T} \right\rbrack + \left\lbrack {V^{c}\bigcap T^{c}} \right\rbrack}{\left\lbrack {V\bigcup T} \right\rbrack + \left\lbrack {V^{c}\bigcap T^{c}} \right\rbrack};$V represents the VOA; T represents the second volume; T^(c) represents aportion of an area in which the second volume is not present; V^(c)represents a portion of the area in which the VOA is not present; ∩represents intersection; and ∪ represents union.
 10. The system of claim1, wherein the first score includes a first sub-score that representsthe amount by which the VOA overlaps the second volume and a secondsub-score that represents the amount of the VOA that does not overlapthe second volume, the first and second sub-scores being output.
 11. Thesystem of claim 10, wherein: the generating of the first sub-scoreincludes calculating $\frac{V\bigcap T}{T};$ the generating of thesecond sub-score includes calculating $\frac{V\bigcap T^{c}}{T^{c}};$ Vrepresents the VOA; T represents the second volume; T^(c) represents aportion of an area in which the second volume is not present; and ∩represents intersection.
 12. The system of claim 10, wherein the actionsfurther comprise plotting the first and second sub-scores as a singlecoordinate on a graph, a first axis of the graph corresponding topossible values of the first sub-score and a second axis of the graphcorresponding to possible values of the second sub-score.
 13. The systemof claim 12, wherein the plotted coordinate representing the first andsecond sub-scores is one of a plurality of plotted coordinates plottedin the graph, others of the plotted coordinates representing respectivepairs of sub-scores calculated for other sets of stimulation parameters.14. The system of claim 13, wherein the actions further comprisedisplaying in the graph a curve formed by connecting the plottedcoordinates.
 15. The system of claim 14, wherein the actions furthercomprise: automatically selecting, by the processor and based on acharacteristic of the curve, one of the sets of stimulation parametersfor which coordinates have been plotted in the graph; and outputting theselected set of stimulation parameters.
 16. The system of claim 1,wherein the actions further comprise outputting the first score.
 17. Thesystem of claim 1, wherein the actions further comprise, for each of aplurality of additional VOAs, generating a first score for theadditional VOA based on a) an amount by which the additional VOAoverlaps the second volume and b) at least one of the following listedquantities: 1) a size of the second volume; 2) a size of an area formedby combination of the additional VOA and the second volume, 3) a size ofa predetermined area excluding both the additional VOA and the secondvolume, 4) an amount of the additional VOA that does not overlap thesecond volume, or 5) an amount of the second volume that does notoverlap the additional VOA; wherein each of the additional VOAs is avolume of tissue estimated to be activated by stimulation providedaccording to a different set of stimulation parameters.
 18. The systemof claim 17, wherein the actions further comprise receiving a userselection of one of the VOA or additional VOAs; and upon user request,outputting a set of stimulation parameters corresponding to the selectedone of the VOA or additional VOAs to initiate stimulation of patienttissue using a leadwire implanted in the patient tissue.
 19. The systemof claim 17, wherein the actions further comprise: automaticallyselecting one of the VOA or additional VOAs based on the first scores;and outputting a set of stimulation parameters corresponding to theselected one of the VOA or additional VOAs to initiate stimulation ofpatient tissue using a leadwire implanted in the patient tissue.
 20. Anon-transitory computer-readable medium having instructions storedthereon, the instructions comprising: obtain a volume of activation(VOA) of tissue estimated to be activated by stimulation providedaccording to a set of stimulation parameters; obtain a second volume;generate a first score for the VOA based on a) an amount by which theVOA overlaps the second volume and b) at least one of the followinglisted quantities: 1) a size of the second volume; 2) a size of an areaformed by combination of the VOA and the second volume, 3) a size of apredetermined area excluding both the VOA and the second volume, 4) anamount of the VOA that does not overlap the second volume, or 5) anamount of the second volume that does not overlap the VOA; and upon userrequest, output a set of stimulation parameters corresponding to the VOAto initiate stimulation of patient tissue using a leadwire implanted inthe patient tissue.